Next Article in Journal
Development of an Anti-Idiotypic VHH Antibody and Toxin-Free Enzyme Immunoassay for Ochratoxin A in Cereals
Previous Article in Journal
Using Advanced Spectroscopy and Organic Matter Characterization to Evaluate the Impact of Oxidation on Cyanobacteria
Open AccessArticle

The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

1
Pharmacology Department, Amiens University Hospital, 80000 Amiens, France
2
MP3CV Laboratory, EA7517, University of Picardie Jules Verne, 80000 Amiens, France
3
Nephrology Department, Amiens University Hospital, 80000 Amiens, France
4
Department of Nephrology and Dialysis, AURA Nord Saint Ouen, 93400 Saint Ouen, France
5
Nephrology Department, Bordeaux University Hospital, 33000 Bordeaux, France
6
Clinical Inverstigation Center, Aix Marseille University, 13354 Marseille, France
7
Dept Nephrology, Université de Lyon, Hospital Lyon Sud, F-69495 Pierre-Benite, France
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(5), 279; https://doi.org/10.3390/toxins11050279
Received: 4 May 2019 / Revised: 9 May 2019 / Accepted: 10 May 2019 / Published: 17 May 2019
High serum levels of gut-derived uremic toxins, especially p-cresyl sulfate (pCS), indoxyl sulfate (IS) and indole acetic acid (IAA), have been linked to adverse outcomes in patients with chronic kidney disease (CKD). Sevelamer carbonate could represent an interesting option to limit the elevation of gut-derived uremic toxins. The aim of the present study was to evaluate the adsorptive effect of sevelamer carbonate on different gut-derived protein-bound uremic toxins or their precursors in vitro, and its impact on the serum levels of pCS, IS and IAA in patients with CKD stage 3b/4. For the in vitro experiments, IAA, p-cresol (precursor of pCS) and indole (precursor of IS), each at a final concentration of 1 or 10 µg/mL, were incubated in centrifugal 30 kDa filter devices with 3 or 15 mg/mL sevelamer carbonate in phosphate-buffered saline at a pH adjusted to 6 or 8. Then, samples were centrifuged and free uremic toxins in the filtrates were analyzed. As a control experiment, the adsorption of phosphate was also evaluated. Additionally, patients with stage 3b/4 CKD (defined as an eGFR between 15 and 45 mL/min per 1.73 m2) were included in a multicenter, double-blind, placebo-controlled, randomized clinical trial. The participants received either placebo or sevelamer carbonate (4.8 g) three times a day for 12 weeks. The concentrations of the toxins and their precursors were measured using a validated high-performance liquid chromatography method with a diode array detector. In vitro, regardless of the pH and concentration tested, sevelamer carbonate did not show adsorption of indole and p-cresol. Conversely, with 10 µg/mL IAA, use of a high concentration of sevelamer carbonate (15 mg/mL) resulted in a significant toxin adsorption both at pH 8 (mean reduction: 26.3 ± 3.4%) and pH 6 (mean reduction: 38.7 ± 1.7%). In patients with CKD stage 3b/4, a 12-week course of treatment with sevelamer carbonate was not associated with significant decreases in serum pCS, IS and IAA levels (median difference to baseline levels: −0.12, 0.26 and −0.06 µg/mL in the sevelamer group vs. 1.97, 0.38 and 0.05 µg/mL in the placebo group, respectively). Finally, in vitro, sevelamer carbonate was capable of chelating a gut-derived uremic toxin IAA but not p-cresol and indole, the precursors of pCS and IS in the gut. In a well-designed clinical study of patients with stage 3b/4 CKD, a 12-week course of treatment with sevelamer carbonate was not associated with significant changes in the serum concentrations of pCS, IS and IAA. View Full-Text
Keywords: sevelamer; uremic toxins sevelamer; uremic toxins
Show Figures

Figure 1

MDPI and ACS Style

Bennis, Y.; Cluet, Y.; Titeca-Beauport, D.; El Esper, N.; Ureña, P.; Bodeau, S.; Combe, C.; Dussol, B.; Fouque, D.; Choukroun, G.; Liabeuf, S. The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Toxins 2019, 11, 279.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop